About this Author

College chemistry, 1983

The 2002 Model

After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases.
To contact Derek email him directly: derekb.lowe@gmail.com
Twitter: Dereklowe

December 19, 2012

More on the Parabon NSF Press Release

Posted by Derek

Well, I've been away from the computer a good part of the day, but I return to find that the author of the NSF press release that I spoke unkindly of has shown up in the comments to that post. I'm going to bring those up here to make sure that his objections get a fair hearing:

I wrote this press release, and I am a bit concerned that instead of discussing the research with myself, or more importantly the researchers, you decide to attack the text.

We presented information based on research that has been underway for some time, at least two years with NSF peer-reviewed support.

Additionally, we were careful to not overstate either the technology or the impact, but to present an illustration of what the technology can do in the limited space that a press release allows.

A journalist is expected to follow the initial reading of the press release with questions for the researchers involved -- not attack the limited text that we provide as an introduction.

In my eleven years at NSF, I have never had someone attack my work -- particularly without first getting their facts straight.

Please contact the researchers to discuss the technology and limit your criticism for those thongs for which you are informed.

I'm fear that's where the discussion will go next, but if you do wish to learn more about the actual research you are disparaging, please do contact the researchers to learn more about the technology and the approach.)

Several regular readers have already responded in the comments section to that earlier post, making the point that experienced drug discovery scientists found the language in the press release hard to believe (and reminiscent of overhyped work from the past). Josh Chamot's response is reproduced here:

Thank you for the thoughtful responses. This is exactly the engagement I was hoping for.

First, I agree that hype is never what we want to communicate -- and I appreciate that skepticism is critical to ensuring accuracy and the complete communication of news. However, I do hope many of you will explore the research further so that any skepticism is completely informed.

I want to be clear that I have no intention of misleading the research or pharma communities, nor do I want to give false hope to those who might need any of the treatments that we referenced. Our language was intended to convey that the breakthrough to date is exciting, but clearly more work is needed before this can start producing drugs for patients -- and I believe we stated this.

Through links to additional information (such as the full patent application) and clear contact information for the principal investigator, it is our hope that the primary audience for the press release (reporters) will present a thorough and complete account of the work.

We do not wish to mislead, but we also cannot convey a full news story in press release format. The intent is to serve as an alert, and importantly, an accurate one.

Journalists are the primary audience for the press releases, and our system of information is reliant on their services. To the best of my knowledge, the information we presented on Parabon is accurate and states only results that Parabon has demonstrated and announced in their patent application -- the starting point for a journalist to explore the story further.

As background, the pieces I work on cover research efforts that are originally proposed to NSF in a review process informed by peers in the community. Parabon has received both Phase I and Phase II NSF small business funding, so they had succeeded in that competitive peer review twice.

That setting served as a baseline to inform my office that the research approach was a valid starting point -- however, as with almost all NSF research, this is research at the very earliest stages. I can accept that while I wrote the release to reflect this, I was not successful in conveying this clearly. However, the assertions that data in support of the research effort do not exist are incorrect.

The company first came to our office (public affairs) more than two years ago, and it is only now that the company had enough publicly available information for us to pull together an announcement of the technology and some introduction of how it works.

I have some lessons learned here in how to try to clarify caveats, but I stand by my original assertion that the research is valid and exciting. While I have no way to predict Parabon's ultimate success, I do believe that public discussion of their technique can only prove of value to the broader drug development effort -- including the identification of any obstacles that this, or a similar technique, must overcome.

Best,
Josh Chamot

I think what I'll do now is close off the comments to the previous post and have things move over to this entry, with appropriate pointers, so we don't have two discussion going on at the same time. Now, then. I'm not blaming Mr. Chamot for what went out on the wires, because I strongly suspect that he worked with what he was given. It's the people at Parabon that I'd really like to have a word with. If the press release is an accurate reflection of what they wanted to announce, then we have a problem, and it's not with Jack Chamot.

I realize that a press release is, in theory, supposed to be for the press - for reporters to use as a starting point for a real story. But how many of them do that, versus just rewording the release a bit? There are reporters who could pick up on all the problems, but there are many others who might not. The information in the Parabon release, as it stands, makes little sense to those of us who do drug discovery for a living, seems full of overstated claims, and raises many more questions than it answers. Specialists in the field (as many readers here are) will have an immediate and strong reaction to this sort of thing.

And that's one of the purposes of this blog (and of many others): to bring expertise out into the open, to provide people within some specialized area a chance to talk with each other, and to provide people outside it (anyone at all) a chance to sit in and learn about things they otherwise might never hear discussed. I think that the process that Mr. Chamot has described is an older one: scientists describe a discovery of theirs to some sort of press officer, who puts into some useful and coherent form in order to get the word out to reporters, who then can contact the people involved for more details as they write up their stories for a general readership. That's fine, but these days that whole multistep procedure is subject to disintermediation. And that's what we're seeing right now.

It appears that Josh Chamot is learning what I thought was common knowledge. This site is not journalism but rather, "journalism" and is relegated to "drug discovery" scientists bashing anything that doesn't come from them. Because, we all know (or have been told on this site) that only these people know science (even though >98% of them - including the head of the blog have never put a drug on the market, let alone in the clinic).

Josh Chamot is possibly also learning a lesson in media communications. It is not uncommon for the "experts" in the press office of a company or university to suggest alterations to a press release in order to "more effectively communicate" the underlying science. Scientists are after all just a bunch of nerds who don't understand the "real world"... (sarcasm)

I had an experience myself where I regret acceding to the recommendations of the press office at my place of work. What went out was more sensationalist, and (in my view) actually less interesting than what had actually been done.

I'm now wiser and will stand my ground when faced with "expert" media advice.

@Lyle Langley: "This site is not journalism but rather, "journalism" and is relegated to "drug discovery" scientists bashing anything that doesn't come from them. Because, we all know (or have been told on this site) that only these people know science"

I'm neither a drug discovery scientist, nor a journalist, nor a chemist, nor a doctor, and I found the claims being made by/for Parabon incoherent at best. The science underneath might be perfectly valid and useful, but it's impossible to tell this based on what we've seen so far. If hand-waving press releases and patent applications are suitable substitutes for actual data and results, what's the point of being a scientist anyway?

I do not understand why there is so much confusion. Clearly, they had a top-flight talent recruiting firm lure away, with promises of fame and fortune, the most skilled Oompa-Loompas from Willy Wonka's Factory. Now, instead of making chocolate, the Oompa-Loompas are constructing molecules one atom at a time and singing some nice tunes as they work.

I'm afraid you have it quite wrong. All of these "lost souls" in drug discovery would really love to have a better way. What we don't need more of is overhyped BS -- we've had quite enough of that.

And as one who has helped to put several drugs into the clinic I can tell you that this is really luck, not skill. You happen to be on programs that are successful, supported all the way by management, don't have unanticipated toxicity, etc.

By this metric Parabon would be doomed, too, as their management has pretty much nothing in the way of drug discovery. But, hey, I hope it works. Maybe in a few years the same press release can go out with actual evidence behind it, and you will see on this board cheering and congratulations all around.

@#1: I'm not sure if you're trolling or not, but under the assumption that you are serious, I wish to offer some feedback on your points.

1) 'This site is not journalism but rather, "journalism" and is relegated to "drug discovery" scientists bashing anything that doesn't come from them.'

I do not recall, in the several years that I have followed this blog, that Mr. Lowe considered himself a 'journalist' in the traditional sense. I do believe that his intention is to bring together educated scientists (not just drug discovery people) to discuss the 'talking points' of modern science. I believe that the purpose is to allow for discourse on each particular topic. Issues such as the press release in question is not to "bash" it because it didn't come from one of us, but to highlight a fatal flaw in society/science relations. Such flaws must be fixed for social harmony with science to occur.

As for "bashing" in general, I would argue that it is our duty to question every single piece of scientific data that comes across our path. By becoming lax in our efforts to inspect the science which is done daily, we allow many things to pass by, including fraud and crappy procedures which don't work correctly. Only a non-scientist would label in-the-trenches science "bashing," in my opinion.

2) 'Because, we all know (or have been told on this site) that only these people know science (even though >98% of them - including the head of the blog have never put a drug on the market, let alone in the clinic).'

We (the readership and author of this blog) are not the only ones who know science. In fact, many times I find myself describing this blog to my co-workers, who have never visited it. I also do not believe that Mr. Lowe has ever stated that we are the only ones who know science. I would of course admit fault if such an entry was presented.

Although I do not know where 98% came from, I believe the vast majority of drug discovery scientists do not discover marketable compounds. That does not, however, mean that they do not know what they are doing, or have inferior knowledge of science. Again, I do not believe any scientist with any vague knowledge of the process would say this.

I am open to your suggestions and rebuttals, but I beg that you please do not make sweeping generalizations which are quite inaccurate.

My favorite bit is Mr. Chamot's admonition that "you limit criticism for those things which you are informed"

Is that not the purpose of a press release, to inform?

The criticism is that the press release failed to do that in any meaningful way.

At a minimum a press release should provide enough information such that it makes people want to learn more. The only thing this press release did was make me want nothing to do with Parabon and wonder what the hell the NSF was spending its money on. It's probably a good bet that was not the effect Mr. Chamot or his supervisor's were hoping the press release would illicit. I will say, however, it does have us discussing Parabon.

He then churlishly goes on to bemoan the oncoming spelling police which he believes will be next from the blog's readership.

True or not, insulting people as ignorant and petty is usually not a good strategy.

Just wanted to go on record to say that, although indeed I haven't put any drugs on the market (given that I'm not in any shape or form involved in the drug discovery process that would be difficult), I greatly enjoy reading In The Pipeline and the way it's delivered. One would expect that strong opinions on medicinal chemistry would come from medicinal chemists, particularly when there is a valid reason for distress... One thing I like about Derek's writing is that he is absolutely matter-of-fact about things, and not overhyping any menial discovery. The attack by Lyle seems incredibly juvenile, and unwarranted.

In the interest of learning a bit more about the topic in question, I just visited the Parabon website.

Once I got beyond the exuberant fluff one finds posted on the websites of all infant biotech/chemotech companies, it appeared to me that Parabon is attempting to develop highly ordered DNA structures for use as both drug delivery vehicles and as aptamers.

Their management team is comprised of a computer scientist, a chemist, and an engineer, none of whom have any documented drug development experience.

Others should delve into the company website and post their perspectives here.

When did press releases become a private matter between journalists and the principals mentioned in the press release? I see the text quoted on the NSF.gov website--is that only for journalists to access? I'll bet the press release is sent to anybody who follows the NSF, far more than just journalists. Any press release is sent out for public consumption these days. Trying to blame Derek Lowe for not doing some sort of journalistic due diligence, to try to make sense of fanciful claims by carefully researching the company, is ridiculous: he brought it up, like a conversation around the water cooler, and people weighed in. The problem was not that participants were clueless about how that sort of thing might work (THAT's what journalists usually go to the principals for), it was knowing how that sort of thing generally works and trying to make sense of the grandiose claims. The problem is, when a complicated story has been simplified for a less educated audience, it should still be recognizable to a more educated audience. And, beyond recognizable--dare I even hope?--have a grain of truth.

Of those two criteria, understandability and accuracy, I would assign blame to the press release writer only for the first (and perhaps even only part there). Unlike one of the other commenters, I suspect the blame for accuracy goes to the researchers.

After all, the quotes provided in the original post were not merely from the PR, but quotes from the mouths of the principal researchers. Blarney and hype seem to be just part of the research business nowadays, and as I said before, it's a slippery slope from saying what things this might conceivably let us start thinking about being able to do, to saying it will let us do those things. In research PR land, we'll be motoring around in simultaneously fusion- and solar-powered, cloaked, wormhole-creating, greenhouse-gas-absorbing, self-driving, flying cars in a couple of years, once these advancements hit the market.

As Derek Lowe pointed out then, atom-by-atom synthesis is NOT possible by this DNA framework; instead Parabon takes the small molecule drugs provided by pharmaceutical companies (that is, painstakingly researched and tested in the old fashioned way) or antibodies, and incorporate them in their framework. Nor has Parabon somehow created a rational, methodical design process for pharmaceuticals; instead, given a pharmaceutical, they promise a rational, methodical design process for making their framework--an extra framework which for most pharmaceuticals isn't necessary or even desired.

If the researchers at Parabon decide to join in, I'd ask (actually, second the questions Derek asked):
1. Essemblix final products: always injectable delivery?
2. Targeted to cell surfaces? This "transfection" process of delivery, has it been shown in vivo from an Essemblix framework? How does that work?
3. What sorts of ADME properties do the various sizes of Essemblix frameworks have?

Perhaps it would be better to ask at Janssen Pharmaceuticals, who is apparently testing their PJ-01 candidate for prostate cancer. Parabon's other drug, P24RDN, is also targeted at cancer (GBM).

So the way I read this is that press releases are intentionally uninformative, and to find out the truth its up to the reader to pick up the phone and talk to the original investigators? And, in this case, the press release was written in such a way that anyone who would actually care is inspired to say only "Bleh, who cares."

Why issue this sort of press release at all? If this was real science news it would have real results. The only other conclusions are the cynical ones everyone is reaching, about a fool and his money, or maybe as a way to provide justification for how grant monies were allocated.

The tech' side is easy to understand, although not realistic. It's DNA nanoobjects (Seeman like) of limited size displaying antibodies/aptamers and small molecule drugs. They can be created at will, i.e., you can have custom made aptamers/antibody fragments, combined with small molecule drugs, both being chosen and assembled into structures on spot, into different targeting moieties (immunotoxins). It's not realistic, not likely to cure anyone, not likely to ever pass through FDA, not likely to attract private money, not much different than traditional immunotoxins, and not likely to get anyone rich, but, it's in its own way a step in the right direction. Someone may even mention it in a century or two as the first of something company.

I think it's actually the job of NSF to invest money in things like this.

p.s. CoI statement: Nothing to do with company, never heard of it before this blogging events, but happen to know some of the scientific founders and they are fine gentlemen.

Full marks for entering the dialog and learning some lessons, speaks highly of you.

I would say, though, that the idea that a press release is aimed information for journalists is an idea that does not make sense today. Maybe when they came across a 'wire' into press offices for distribution in newspapers, but not today. I read them constantly for info about new and exciting technologies that could be the source of new research or new companies. As such, I and other scientists, investors, even patients read press releases to extract useful information. The Parabon release, due to comments of the principals, is one of the worst I have seen. You were misled. perhaps finding an outside expert to comment would have been a good idea.

You reframe: the research is valid and exciting, is hardly the stuff that warrants a press release. Further, discussion of what the technology must overcome would have made the press release informative. Have you ever heard of basic research that did not, in the context of grant applications or press releases, claim to make great impact? Go to almost any journal and read the last paragraph of papers...These findings may some day improve the diagnosis and treatment of...

As more academic researcher move into the drug discovery or translation area of research, expect more claims parallel to the wonder drugs of a century ago- tonics that 'cure what ails you'. We need more journalists and skeptics to reign in the exuberant optimism associated with securing funding rather than being a tool to deliver the hype.

In sum, I think you and others have an important job to do, and I suppose others who have joined the chorus of criticism think so as well. In the future, please call upon us with experience to help you 'decode' the language of the invested parties prior to being the messenger. Many here would be delighted to help, I am sure.

I assumed that you could use the DNA itself as a targeting moiety - if it targets a sequence found in a patient's cancer (and not elsewhere - tumor promoter genes, specific mutations determined by individual screening, etc.) and you can make a complementary sequence that doesn't bind the DNA of the nanostructure as well as the target DNA, then you can use the DNA (with appropriate toxins attached - an intercalator? reductively-activated DNA alkylator?) to put an antitumor compound where you want it.

That would require, among other things, efficient delivery to target cell nuclei. There's currently no way to do that for such assemblies, and I wouldn't hold my breath for one soon. Viruses can do it, of couse, but viral therapies haven't exactly been burning through the regulatory approval process, have they? And I don't see any reason to use self-assembling DNA scaffolds in combination with viral delivery anyway.

As for targeting cancer-specific sequences, I'm doubtful. If the sequence is a rearrangement, and you can target the junction of two sequences that aren't contiguous in healthy cells, maybe. But if the alteration is a point mutation, the energetics are likely to be problematic. Anything less than ~17 bases and your target sequence is likely to exist more than once in the genome just by chance. At or above 17 bases, a single mismatch won't be sufficient to prevent hybridization to the normal sequence under physiological conditions.

It didn't seem probable, but that seemed consistent with the depiction on CJ's blog of Parabon's research. I don't know how you would make them permeable, and if you don't have base pairing, I don't know if you can make structures of DNA to specifically bind cancer-specific extracellular targets (cell receptors?) better than antibodies or something else.

I'm sorry, but doesn't Josh Chamot understand that people like me realize (or at least know based on the evidence) that journalists essentially don't exist and that most press releases are less than useful? As a media officer for the NSF that is troubling.

I'm not an expert in this field. That's why I read blogs by experts. So they can tell me things that "journalists" or more correctly stenographers won't or can't. I have an entirely different (and more accurate) view of the industry because of this blog. One that I wouldn't (or couldn't) have because of "the media".

Finally, if you can't summarize the research accurately, then don't. If you do anyway and it's a job requirement, then you aren't good at your job. There is no reason that press releases have to be limited to a specific size in the era of the web, unless style is more importance than substance. You'd think someone from the National SCIENCE Foundation would get that, especially if they were the Media Officer for ENGINEERING.

You can make DNA aptamers specific for tumor-related cell surface markers. There are plenty of research papers to that effect. So yes, in principle, you can use DNA in place of antibodies. However, I know of only one approved aptamer-based therapeutic (pegaptanib/Macugen), versus the many dozens of approved antibodies.

If your press release cannot at least clearly outline even the basic premise of what you are doing to the audience in question, then either

you are not a good writer, you chose to mail it in on that instance, you don't understand it yourself, or you are covering something up.

I'm a scientist and my wife is not. I have almost been able to get across the "big picture" of what I am working on to her. If I couldn't, then I'd have to wonder if what I was doing isn't really that significant.

I have finally read the original press release and, having some background, it's not actually bad. Here it is translated:

it's well known that there is an RNA aptamer (modified) that targets prostate cancer cell lines. So, they put it in DNA nanostructure together with some toxin and managed to kill cells. This is actually highly expected, because this same aptamer has been used for years, and it's known to carry pretty much anything you attach to it inside prostate cancer cells.

Atom-by-atom terminology is taken from Seeman's crystal structures, in which he demonstrated that he can have predictable positions of individual atoms (from crystallography perspective) based on his designs. It's real, it's in Nature, and no, it will not be retracted, because it's real. It's actually kind of rational drug design in this case, but not in a way traditional med-chemist would look at it, and atom-by-atom is misleading from their perspective. So, therein lies the confusion.

Overall, not that bad, I have to say, different cultures clashing, and producing some confusion. Josh did a nice job here, I think, considering difficulty of topic.

M.

p.s. CoI statement: Nothing to do with company. Know a bit about both DNA nanotech and drug discovery.

Creating DNA sequences ins't big news at all. Nor with whatever cool interface. However applying those sequences via injection is something else. Those DNAs, if cDNAs may target some important microRNAs. But truth be told first you have to guess how to make it work in blood conditions (stability and binding).

For funding, research and peer finding please refer to the non-profit Aging Portfolio.

For those on this site who know me only from this press release, you should know my intention is always to encourage engaged discussions about the topics we feature. So this is all a good thing.

Most of my releases are more focused on academic research, and controversies can be heated as experts in the field debate the specifics of findings. Those discussions have been based not on my releases, but the research papers that tie to those releases. Again, I try to be a conduit, not the final word.

In this case, the focus of my release was not just the research, but instead a desire to highlight another lesser-known (hence the need to publicize it) aspect of NSF support, that being our support for small businesses addressing complex research challenges.

Mea culpa on not incorporating more of the research description from the patent application (which is linked from the press release, and I include it again here:

I had made the assumption that, as with academic research that I have covered, those with concerns would read the original document -- in this case the patent application.

What came across as my thin-skinned response (and it was/is) was a plea that the conversation continue, but as an informed discussion that addresses the detailed information in the patent. That has value for everyone involved, including I imagine the folks at Parabon.

In retrospect, I agree that what I published regarding the research elements is far too abridged. Again, my intention with this particular release (unlike those I have crafted on areas of science and technology) was to inform the public that there are federal programs available for small businesses that enable those businesses to engage technical challenges, which if met, can help the business achieve greater impact. In the future, I will endeavor to add more technical information about the specific research effort.

Keep up the discussion, and the critical attention, but please do so with a purpose of moving the knowledge forward.

What was upsetting was the personal attack, not the argument for more information. And this is the thin-skinned part: Many individuals who know me by nothing more than this release personally attacked me for "trash science", and they had not looked at the in-depth content presented in the patent materials. And yes, it was upsetting, particularly as most of it came from folks anonymously posting under pseudonyms (I always include my full name and contact information).

This is partly my point in engaging you -- just because this is a blog doesn't mean that conversation degrades to that level. It doesn't advance the research, and it doesn't help improve much of anything, nor does it give me anything actionable I can use to improve future press releases.

The conversation will continue, and I again encourage you to contact the researchers at Parabon with your most pressing concerns as they will have the technical knowledge that I do not.